An innovative phase 2 proof-of-concept trial design to evaluate SAR445088, a monoclonal antibody targeting complement C1s in chronic inflammatory demyelinating polyneuropathy

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare immune-mediated disease of the peripheral nerves, with significant unmet treatment needs. Clinical trials in CIDP are challenging; thus, new trial designs are needed. We present design of an open-label phase 2 study (NCT04658472) eva...

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Autores: Querol, Luis|||0000-0002-4289-8264, Lewis, Richard Alan|||0000-0002-1140-4575, Hartung, H.P., van Doorn, Pieter|||0000-0003-2584-3357, Wallstroem, E., Luo, Xiaodong|||0000-0002-8214-9874, Alonso-Alonso, Miguel|||0000-0003-3372-9933, Atassi, Nazem, Hughes, Richard|||0000-0001-5251-3797
Formato: artículo
Fecha de publicación:2023
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:301690
Acesso em linha:https://ddd.uab.cat/record/301690
https://dx.doi.org/urn:doi:10.1111/jns.12551
Access Level:acceso abierto
Palavra-chave:Bayesian analysis
CIDP
SAR445088
Complement C1s
Complement classical pathway
Trial design
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spelling An innovative phase 2 proof-of-concept trial design to evaluate SAR445088, a monoclonal antibody targeting complement C1s in chronic inflammatory demyelinating polyneuropathyQuerol, Luis|||0000-0002-4289-8264Lewis, Richard Alan|||0000-0002-1140-4575Hartung, H.P.van Doorn, Pieter|||0000-0003-2584-3357Wallstroem, E.Luo, Xiaodong|||0000-0002-8214-9874Alonso-Alonso, Miguel|||0000-0003-3372-9933Atassi, NazemHughes, Richard|||0000-0001-5251-3797Bayesian analysisCIDPSAR445088Complement C1sComplement classical pathwayTrial designChronic inflammatory demyelinating polyneuropathy (CIDP) is a rare immune-mediated disease of the peripheral nerves, with significant unmet treatment needs. Clinical trials in CIDP are challenging; thus, new trial designs are needed. We present design of an open-label phase 2 study (NCT04658472) evaluating efficacy and safety of SAR445088, a monoclonal antibody targeting complement C1s, in CIDP. This phase 2, proof-of-concept, multicenter, open-label trial will evaluate the efficacy, and safety of SAR445088 in 90 patients with CIDP across three groups: (1) currently treated with standard-of-care (SOC) therapies, including immunoglobulin or corticosteroids (SOC-Treated); (2) refractory to SOC (SOC-Refractory); and (3) naïve to SOC (SOC-Naïve). Enrolled participants undergo a 24-week treatment period (part A), followed by an optional treatment extension for up to an additional 52 weeks (part B). In part A, the primary endpoint for the SOC-Treated group is the percentage of participants with a relapse after switching from SOC to SAR445088. The primary endpoint for the SOC-Refractory and SOC-Naïve groups is the percentage of participants with a response, compared to baseline. Secondary endpoints include safety, tolerability, immunogenicity, and efficacy of SAR445088 during 12-week overlapping period (SOC-Treated). Part B evaluates long-term safety and durability of efficacy. Data analysis will be performed using Bayesian statistics (predefined efficacy thresholds) and historical data-based placebo assumptions to support program decision-making. This innovative trial design based on patient groups and Bayesian statistics provides an efficient paradigm to evaluate new treatment candidates across the CIDP spectrum and can help accelerate development of new therapies.Universitat Autònoma de Barcelona 22023-01-0120232023-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/301690https://dx.doi.org/urn:doi:10.1111/jns.12551reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3016902026-06-06T12:50:31Z
dc.title.none.fl_str_mv An innovative phase 2 proof-of-concept trial design to evaluate SAR445088, a monoclonal antibody targeting complement C1s in chronic inflammatory demyelinating polyneuropathy
title An innovative phase 2 proof-of-concept trial design to evaluate SAR445088, a monoclonal antibody targeting complement C1s in chronic inflammatory demyelinating polyneuropathy
spellingShingle An innovative phase 2 proof-of-concept trial design to evaluate SAR445088, a monoclonal antibody targeting complement C1s in chronic inflammatory demyelinating polyneuropathy
Querol, Luis|||0000-0002-4289-8264
Bayesian analysis
CIDP
SAR445088
Complement C1s
Complement classical pathway
Trial design
title_short An innovative phase 2 proof-of-concept trial design to evaluate SAR445088, a monoclonal antibody targeting complement C1s in chronic inflammatory demyelinating polyneuropathy
title_full An innovative phase 2 proof-of-concept trial design to evaluate SAR445088, a monoclonal antibody targeting complement C1s in chronic inflammatory demyelinating polyneuropathy
title_fullStr An innovative phase 2 proof-of-concept trial design to evaluate SAR445088, a monoclonal antibody targeting complement C1s in chronic inflammatory demyelinating polyneuropathy
title_full_unstemmed An innovative phase 2 proof-of-concept trial design to evaluate SAR445088, a monoclonal antibody targeting complement C1s in chronic inflammatory demyelinating polyneuropathy
title_sort An innovative phase 2 proof-of-concept trial design to evaluate SAR445088, a monoclonal antibody targeting complement C1s in chronic inflammatory demyelinating polyneuropathy
dc.creator.none.fl_str_mv Querol, Luis|||0000-0002-4289-8264
Lewis, Richard Alan|||0000-0002-1140-4575
Hartung, H.P.
van Doorn, Pieter|||0000-0003-2584-3357
Wallstroem, E.
Luo, Xiaodong|||0000-0002-8214-9874
Alonso-Alonso, Miguel|||0000-0003-3372-9933
Atassi, Nazem
Hughes, Richard|||0000-0001-5251-3797
author Querol, Luis|||0000-0002-4289-8264
author_facet Querol, Luis|||0000-0002-4289-8264
Lewis, Richard Alan|||0000-0002-1140-4575
Hartung, H.P.
van Doorn, Pieter|||0000-0003-2584-3357
Wallstroem, E.
Luo, Xiaodong|||0000-0002-8214-9874
Alonso-Alonso, Miguel|||0000-0003-3372-9933
Atassi, Nazem
Hughes, Richard|||0000-0001-5251-3797
author_role author
author2 Lewis, Richard Alan|||0000-0002-1140-4575
Hartung, H.P.
van Doorn, Pieter|||0000-0003-2584-3357
Wallstroem, E.
Luo, Xiaodong|||0000-0002-8214-9874
Alonso-Alonso, Miguel|||0000-0003-3372-9933
Atassi, Nazem
Hughes, Richard|||0000-0001-5251-3797
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv Bayesian analysis
CIDP
SAR445088
Complement C1s
Complement classical pathway
Trial design
topic Bayesian analysis
CIDP
SAR445088
Complement C1s
Complement classical pathway
Trial design
description Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare immune-mediated disease of the peripheral nerves, with significant unmet treatment needs. Clinical trials in CIDP are challenging; thus, new trial designs are needed. We present design of an open-label phase 2 study (NCT04658472) evaluating efficacy and safety of SAR445088, a monoclonal antibody targeting complement C1s, in CIDP. This phase 2, proof-of-concept, multicenter, open-label trial will evaluate the efficacy, and safety of SAR445088 in 90 patients with CIDP across three groups: (1) currently treated with standard-of-care (SOC) therapies, including immunoglobulin or corticosteroids (SOC-Treated); (2) refractory to SOC (SOC-Refractory); and (3) naïve to SOC (SOC-Naïve). Enrolled participants undergo a 24-week treatment period (part A), followed by an optional treatment extension for up to an additional 52 weeks (part B). In part A, the primary endpoint for the SOC-Treated group is the percentage of participants with a relapse after switching from SOC to SAR445088. The primary endpoint for the SOC-Refractory and SOC-Naïve groups is the percentage of participants with a response, compared to baseline. Secondary endpoints include safety, tolerability, immunogenicity, and efficacy of SAR445088 during 12-week overlapping period (SOC-Treated). Part B evaluates long-term safety and durability of efficacy. Data analysis will be performed using Bayesian statistics (predefined efficacy thresholds) and historical data-based placebo assumptions to support program decision-making. This innovative trial design based on patient groups and Bayesian statistics provides an efficient paradigm to evaluate new treatment candidates across the CIDP spectrum and can help accelerate development of new therapies.
publishDate 2023
dc.date.none.fl_str_mv 2
2023-01-01
2023
2023-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/301690
https://dx.doi.org/urn:doi:10.1111/jns.12551
url https://ddd.uab.cat/record/301690
https://dx.doi.org/urn:doi:10.1111/jns.12551
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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